What are the doses of methimazole and propranolol (beta blocker) for Pediatric Graves' disease?

Methimazole and Propranolol Dosing in Pediatric Graves' Disease

Methimazole Dosing

For pediatric Graves' disease, the recommended initial dose of methimazole is 0.4-0.7 mg/kg/day, with lower doses being equally effective and causing fewer adverse effects than higher doses. 1, 2, 3

• Initial dosing of 0.4-0.7 mg/kg/day is effective for normalizing thyroid function while minimizing adverse effects 3
• Higher doses (>0.7 mg/kg/day) do not significantly improve time to normalization of thyroid hormone levels but substantially increase adverse effects 1, 3
• Lower doses (<0.7 mg/kg/day) have been shown to normalize free T4 levels in a similar timeframe as higher doses 2
• The goal of therapy is to maintain free T4 or free T4 index in the high-normal range using the lowest possible thioamide dosage 4

Monitoring and Dose Adjustment

• Measure free T4 or free T4 index every 2-4 weeks to guide therapy 4
• Adjust dosage based on thyroid function tests and clinical response 4
• Monitor for adverse effects, which occur more frequently at higher doses 1, 3

Adverse Effects of Methimazole

• Minor adverse effects occur in approximately 9-13% of patients at lower doses (<0.7 mg/kg/day) but increase to over 60% at higher doses 1
• Severe adverse effects like neutropenia are rare at lower doses but increase significantly at doses >0.7 mg/kg/day 3
• Other potential side effects include hepatitis, vasculitis, and thrombocytopenia 4
• Agranulocytosis, a serious side effect, typically presents with sore throat and fever; if these symptoms develop, obtain a complete blood count and discontinue methimazole 4

Propranolol Dosing

Propranolol can be used at 1-2 mg/kg/day divided into 2-3 doses to control symptoms of hyperthyroidism until methimazole reduces thyroid hormone levels. 4, 5

• Propranolol is primarily used to reduce symptoms like tachycardia while waiting for methimazole to take effect 4
• A typical starting dose is 1 mg/kg/day divided into two or three doses 5
• For infantile hemangioma (different indication but provides pediatric dosing reference), the starting dose is 1 mg/kg/day with maintenance dose of 2 mg/kg/day 4
• Maximum dose for non-responders in pediatric patients (based on hemangioma guidelines) is 3 mg/kg/day 4

Monitoring for Propranolol

• Monitor heart rate and blood pressure when initiating therapy 4
• Be cautious in patients with history of hypoglycemic episodes, heart block, or hypersensitivity to propranolol 4
• Once stabilized on an appropriate dose, routine follow-up can occur at 2-3 month intervals 4

Treatment Duration and Considerations

• Treatment with methimazole typically continues for 1-2 years before attempting to discontinue therapy 5
• Long remission can be achieved even in younger prepubertal children 5
• For patients with serious allergic reactions to methimazole, antihistamine therapy may allow continued treatment with methimazole in cases where radioactive iodine or surgery is not preferred 6

Common Pitfalls and Caveats

• Using doses of methimazole >0.7 mg/kg/day significantly increases risk of adverse effects without improving efficacy 1, 3
• Failure to monitor for signs of agranulocytosis (sore throat, fever) can lead to serious complications 4
• Propranolol should be used with caution in patients at risk for hypoglycemia 4
• Suppression of fetal and neonatal thyroid function can occur with thioamide therapy for maternal Graves' disease, but it is usually transient 4